Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Wita Stwosza 63, 80-308 Gdansk, Poland.
Department of Molecular Biotechnology, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland.
Int J Mol Sci. 2021 Jan 19;22(2):956. doi: 10.3390/ijms22020956.
Klotho was initially introduced as an antiaging molecule. Klotho deficiency significantly reduces lifespan, and its overexpression extends it and protects against various pathological phenotypes, especially renal disease. It was shown to regulate phosphate and calcium metabolism, protect against oxidative stress, downregulate apoptosis, and have antiinflammatory and antifibrotic properties. The course of diabetes mellitus and diabetic nephropathy resembles premature cellular senescence and causes the activation of various proinflammatory and profibrotic processes. Klotho was shown to exert many beneficial effects in these disorders. The expression of Klotho protein is downregulated in early stages of inflammation and diabetic nephropathy by proinflammatory factors. Therefore, its therapeutic effects are diminished in this disorder. Significantly lower urine levels of Klotho may serve as an early biomarker of renal involvement in diabetes mellitus. Recombinant Klotho administration and Klotho overexpression may have immunotherapeutic potential for the treatment of both diabetes and diabetic nephropathy. Therefore, the current manuscript aims to characterize immunopathologies occurring in diabetes and diabetic nephropathy, and tries to match them with antiinflammatory actions of Klotho. It also gives reasons for Klotho to be used in diagnostics and immunotherapy of these disorders.
Klotho 最初被介绍为一种抗衰老分子。Klotho 缺乏会显著缩短寿命，而过表达则会延长寿命并预防各种病理性表型，特别是肾脏疾病。它被证明可以调节磷酸盐和钙代谢，保护免受氧化应激，下调细胞凋亡，并具有抗炎和抗纤维化特性。糖尿病及其肾病的病程类似于过早的细胞衰老，并导致各种促炎和促纤维化过程的激活。Klotho 在这些疾病中表现出许多有益的作用。Klotho 蛋白的表达在炎症和糖尿病肾病的早期阶段被促炎因子下调。因此，其治疗效果在这种疾病中减弱。Klotho 的尿液水平显著降低可能是糖尿病肾脏受累的早期生物标志物。重组 Klotho 给药和 Klotho 过表达可能对糖尿病和糖尿病肾病的治疗具有免疫治疗潜力。因此，本文旨在描述发生在糖尿病和糖尿病肾病中的免疫病理学，并尝试将其与 Klotho 的抗炎作用相匹配。它还为 Klotho 在这些疾病的诊断和免疫治疗中的应用提供了依据。
